The purpose of this project is to characterize second messenger pathways involved in receptor regulation of neurotransmitter levels. In the course of examining tyrosine hydroxylase (TH) regulation in mesencephalic mixed neuronal/glial cultures, the microglial activator lipopolysaccharide (LPS) was found to selectively decrease the number of TH-immunopositive neurons. Uptake of [3H]dopamine (DA) was similarly decreased, arguing that these neurons, which are preferentially lost in Parkinson's disease, were being killed by microglial activation rather than the TH being down regulated. TH-immunopositive neurons in olfactory bulb and hypothalamic cultures were less affected than mesencephalic neurons. The classical catecholaminergic neurotoxin 6-OHDA was very effective in killing these dopaminergic neurons in neuron-enriched cultures, but was less effective than LPS in mixed model for studying possible mechanisms involved in Parkinson's disease and neurotoxicity in general.